RANBP2

RAN binding protein 2, the group of Cyclophilin peptidylprolyl isomerases|Nucleoporins|Zinc fingers RANBP2-type |Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 2:108719481-108785810

Previous symbols: [ "ANE1" ]

Links

ENSG00000153201 ∙ NCBI:5903 ∙ OMIM:601181 ∙ HGNC:9848 ∙ Uniprot:P49792 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial acute necrotizing encephalopathy (Strong), mode of inheritance: AD
• familial acute necrotizing encephalopathy (Limited), mode of inheritance: AD
• Leigh syndrome (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Encephalopathy, acute, infection-induced, 3, susceptibility to	AD	Allergy/Immunology/Infectious	Early diagnosis could allow potentially beneficial measures, such as ensuring up-to-date immunization status (eg, against influenza), though full protection against all inciting agents would not be possible	Allergy/Immunology/Infectious; Neurologic	12874403; 19118815; 19811512; 20473521; 21205700

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RANBP2 gene.

• Familial acute necrotizing encephalopathy (759 variants)
• not provided (158 variants)
• Inborn genetic diseases (116 variants)
• not specified (57 variants)
• RANBP2-related condition (6 variants)
• Paramyotonia congenita of Von Eulenburg;Hypokalemic periodic paralysis, type 2;Congenital myasthenic syndrome 16;Potassium-aggravated myotonia;Familial hyperkalemic periodic paralysis (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RANBP2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	179	24	211
missense		1	495	34	23	553
nonsense			11			11
start loss			1			1
frameshift			10			10
inframe indel			7			7
splice donor/acceptor (+/-2bp)			6		1	7
splice region			14	28	4	46
non coding			2	40	11	53
Total	0	1	540	253	59

Variants in RANBP2

This is a list of pathogenic ClinVar variants found in the RANBP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-108719557-C-T			Likely benign (Jun 20, 2018)
2-108719562-C-T		not specified	Benign (Jan 29, 2016)
2-108719566-G-T		not specified • Familial acute necrotizing encephalopathy	Likely benign (Jul 14, 2021)
2-108719608-T-A		Familial acute necrotizing encephalopathy	Uncertain significance (May 20, 2022)
2-108719626-A-C		Familial acute necrotizing encephalopathy	Uncertain significance (Oct 31, 2022)
2-108719658-T-C		Familial acute necrotizing encephalopathy	Uncertain significance (Jul 11, 2022)
2-108719689-C-G		not specified • Familial acute necrotizing encephalopathy	Benign (Oct 03, 2023)
2-108729126-T-A		not specified • Familial acute necrotizing encephalopathy	Benign/Likely benign (Dec 01, 2023)
2-108729131-G-T			Uncertain significance (Dec 23, 2022)
2-108729132-A-G		Familial acute necrotizing encephalopathy	Uncertain significance (Aug 17, 2023)
2-108729139-T-C		Familial acute necrotizing encephalopathy	Uncertain significance (Jun 03, 2019)
2-108729142-A-G		Familial acute necrotizing encephalopathy	Uncertain significance (Jun 03, 2019)
2-108729151-A-G		not specified	Uncertain significance (Dec 06, 2021)
2-108729187-A-T		Familial acute necrotizing encephalopathy	Uncertain significance (Jul 30, 2020)
2-108729208-A-T		Familial acute necrotizing encephalopathy	Likely benign (Mar 10, 2020)
2-108730776-A-T		Familial acute necrotizing encephalopathy	Uncertain significance (Aug 27, 2020)
2-108730784-A-G		Familial acute necrotizing encephalopathy	Uncertain significance (Nov 01, 2019)
2-108730789-C-T		Familial acute necrotizing encephalopathy	Likely benign (Nov 01, 2019)
2-108730806-G-T		Familial acute necrotizing encephalopathy	Uncertain significance (Jul 05, 2022)
2-108730815-A-G		Familial acute necrotizing encephalopathy	Uncertain significance (Jul 05, 2022)
2-108730823-A-G		Familial acute necrotizing encephalopathy	Uncertain significance (Mar 30, 2020)
2-108730850-G-A			Uncertain significance (Apr 02, 2021)
2-108730858-C-G		Familial acute necrotizing encephalopathy	Benign (Aug 17, 2023)
2-108730858-C-T		Familial acute necrotizing encephalopathy	Likely benign (Mar 06, 2021)
2-108730871-G-A		not specified • Familial acute necrotizing encephalopathy	Benign/Likely benign (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RANBP2	protein_coding	protein_coding	ENST00000283195	29	66331

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.79e-13	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.776	1662	1.58e+3	1.05	0.0000807	21232
Missense in Polyphen		283	389.3	0.72694		5321
Synonymous	-2.16	627	562	1.12	0.0000301	6061
Loss of Function	9.61	11	129	0.0856	0.00000691	1788

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000318	0.000308
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000151	0.000141
Middle Eastern	0.000109	0.000109
South Asian	0.0000982	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:22194619, PubMed:15931224). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl- prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}.
• Disease: DISEASE: Encephalopathy, acute, infection-induced, 3 (IIAE3) [MIM:608033]: A rapidly progressive encephalopathy manifesting in susceptible individuals with seizures and coma. It can occur within days in otherwise healthy children after common viral infections such as influenza and parainfluenza, without evidence of viral infection of the brain or inflammatory cell infiltration. Brain T2-weighted magnetic resonance imaging reveals characteristic symmetric lesions present in the thalami, pons and brainstem. {ECO:0000269|PubMed:19118815}. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations in the RANBP2 gene predispose to IIAE3, but by themselves are insufficient to make the phenotype fully penetrant; additional genetic and environmental factors are required (PubMed:19118815). {ECO:0000269|PubMed:19118815}.
• Pathway: RNA transport - Homo sapiens (human);tRNA processing;Disease;Signal Transduction;Gene expression (Transcription);role of ran in mitotic spindle regulation;sumoylation by ranbp2 regulates transcriptional repression;cycling of ran in nucleocytoplasmic transport;Regulation of HSF1-mediated heat shock response;Metabolism of carbohydrates;Rev-mediated nuclear export of HIV RNA;Late Phase of HIV Life Cycle;HIV Life Cycle;Interactions of Rev with host cellular proteins;Host Interactions of HIV factors;HIV Infection;snRNP Assembly;Vpr-mediated nuclear import of PICs;SUMOylation of DNA damage response and repair proteins;Transport of Ribonucleoproteins into the Host Nucleus;Viral Messenger RNA Synthesis;Export of Viral Ribonucleoproteins from Nucleus;SUMOylation of chromatin organization proteins;Influenza Viral RNA Transcription and Replication;Cellular responses to stress;SUMOylation of RNA binding proteins;Post-translational protein modification;SUMOylation of DNA replication proteins;SUMO E3 ligases SUMOylate target proteins;NEP/NS2 Interacts with the Cellular Export Machinery;Metabolism of proteins;Influenza Life Cycle;Influenza Infection;Metabolism of RNA;Glycolysis and Gluconeogenesis;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;Infectious disease;Leukotriene metabolism;Squalene and cholesterol biosynthesis;Purine metabolism;Vitamin B3 (nicotinate and nicotinamide) metabolism;Vitamin B5 - CoA biosynthesis from pantothenate;Metabolism;Transport of the SLBP independent Mature mRNA;Transport of the SLBP Dependant Mature mRNA;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Mature mRNAs Derived from Intronless Transcripts;RHO GTPases Activate Formins;Pyrimidine metabolism;SUMOylation;Glycosphingolipid metabolism;Cellular responses to external stimuli;Regulation of Glucokinase by Glucokinase Regulatory Protein;Glycolysis;RHO GTPase Effectors;Phosphatidylinositol phosphate metabolism;Signaling by Rho GTPases;Lysine metabolism;Methionine and cysteine metabolism;Selenoamino acid metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Aminosugars metabolism;Pentose phosphate pathway;Nuclear Pore Complex (NPC) Disassembly;De novo fatty acid biosynthesis;Glycerophospholipid metabolism;Prostaglandin formation from dihomo gama-linoleic acid;Putative anti-Inflammatory metabolites formation from EPA;Vitamin D3 (cholecalciferol) metabolism;Vitamin E metabolism;tRNA processing in the nucleus;Transport of Mature mRNA derived from an Intron-Containing Transcript;mechanism of protein import into the nucleus;Signaling events mediated by HDAC Class II;Metabolism of non-coding RNA;Cellular response to heat stress;Nuclear Envelope Breakdown;Mitotic Prophase;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Nuclear import of Rev protein;Glucose metabolism;Transcriptional regulation by small RNAs;Cell Cycle;Resolution of Sister Chromatid Cohesion;Interactions of Vpr with host cellular proteins;Glycine, serine, alanine and threonine metabolism;Cell Cycle, Mitotic;Sumoylation by RanBP2 regulates transcriptional repression;Transport of Mature Transcript to Cytoplasm;Signaling events mediated by HDAC Class I;Processing of Capped Intron-Containing Pre-mRNA;Arachidonic acid metabolism;Gene Silencing by RNA (Consensus)

Recessive Scores

• pRec: 0.522

Intolerance Scores

• loftool: 0.481
• rvis_EVS: -1.54
• rvis_percentile_EVS: 3.33

Haploinsufficiency Scores

• pHI: 0.932
• hipred: Y
• hipred_score: 0.712
• ghis: 0.589

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.910

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ranbp2
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype

Gene ontology

• Biological process: protein peptidyl-prolyl isomerization;response to amphetamine;regulation of gluconeogenesis;mRNA export from nucleus;protein folding;NLS-bearing protein import into nucleus;viral process;protein sumoylation;positive regulation of glucokinase activity;positive regulation of GTPase activity;centrosome localization
• Cellular component: nucleus;nuclear envelope;annulate lamellae;nuclear pore;cytoplasm;mitochondrion;cytosol;membrane;nuclear membrane;nuclear inclusion body;nuclear pore cytoplasmic filaments;nuclear pore nuclear basket;cytoplasmic periphery of the nuclear pore complex
• Molecular function: RNA binding;peptidyl-prolyl cis-trans isomerase activity;GTPase activator activity;protein binding;Ran GTPase binding;cyclosporin A binding;SUMO transferase activity;protein-containing complex binding;metal ion binding